Introduction: This study aimed to show the clinical outcomes of implants inserted by guided surgery supporting mandibular overdentures in edentulous patients. Patients and methods: Mandibular edentulous patients were diagnosed with an oral examination, cone-beam computerized tomography, and diagnostic casts for intermaxillary relations and treated with overdentures over two implants by guided surgery. After flapless surgery, implants were early loaded with an overdenture at 6 weeks. Results and discussion: Fourteen patients (nine females and five males) were treated with 28 implants. Four patients (28.6%) had a previous history of periodontitis. Five patients (35.7%) were smokers. Nine patients (64.3%) suffered from systemic diseases (i.e., diabetes, cardiovascular diseases). The clinical follow-up of the study was 44.7 ± 31.4 months. Clinical outcomes showed a global success of 100% of implants. Fourteen overdentures were placed in the patients over the implants. Mean marginal bone loss was 1.25 mm ± 0.95 mm. Four patients (28.6%) showed some kind of mechanical prosthodontic complications. Six implants (21.4%) were associated with peri-implantitis. Conclusions: This study indicates that treatment of mandibular edentulous patients with overdentures by guided surgery and early loading of implants placed appears to be a successful implant protocol.